POS1046 DEUCRAVACITINIB LONG-TERM EFFICACY AND SAFETY IN PLAQUE PSORIASIS: 2-YEAR RESULTS FROM THE PHASE 3 POETYK PSO PROGRAM
Authors: R. B. Warren, H. Sofen, S. Imafuku, J. Szepietowski, A. Blauvelt, L. Spelman, E. Colston, J. Toms, A. Buck, S. Banerjee, A. Menter
Journal: Annals of the Rheumatic Diseases (2022)

Background Tyrosine kinase 2 (TYK2) is an intracellular kinase that mediates signalling of key cytokines (eg, interleukin [IL]-23 and Type I interferons) involved in the pathogenesis of immune-mediated diseases including plaque psoriasis and psoriatic arthritis (PsA). Deucravacitinib is a novel, oral, selective TYK2 inhibitor that achieves high selectivity by uniquely binding to the regulatory domain of the enzyme, rather than to the more conserved active domain. Deucravacitinib showed superior efficacy compared with placebo at 16 weeks in a Phase 2 trial in patients with PsA. 1 The efficacy and tolerability of deucravacitinib in patients with moderate to severe psoriasis were previously demonstrated in 2 pivotal, Phase 3, double-blind trials, POETYK PSO-1 and PSO-2. 2 Objectives To assess the long-term efficacy and safety of deucravacitinib in patients with psoriasis in a Phase 3, open-label, long-term extension (LTE) trial. Methods The 52-week PSO-1 and PSO-2 trials randomised patients with moderate to severe plaque psoriasis 2:1:1 to deucravacitinib 6 mg once daily, placebo, or apremilast 30 mg twice daily. Patients could then enrol in the LTE trial and receive open-label deucravacitinib 6 mg once daily. Results 1221 patients enrolled in the LTE trial and received ≥1 dose of deucravacitinib. Demographic and baseline disease characteristics were balanced across treatment groups; mean age at disease onset was 28.6 years, mean disease duration was 18.9 years, and 18.0% of patients had PsA at baseline. Cumulative exposures in person-years from randomisation in PSO-1 or PSO-2 and the LTE trial were 2166.9 and 2482.0 for efficacy and safety analyses, respectively. At enrolment in the LTE trial, PASI 75 and sPGA 0/1 response rates were 65.1% and 50.9%, respectively, and were maintained for up to 2 years after initial randomisation (Week 48 of LTE; PASI 75: 75.7%; sPGA 0/1: 56.4% [as observed]). Exposure-adjusted incidence rates per 100 person-years for adverse events were similar in the controlled period (Weeks 0–52) of PSO-1 and PSO-2 and during the cumulative PSO-1, PSO-2, and LTE trial period (229.2 [controlled period] vs 154.4 [cumulative period]), serious adverse events (5.7 vs 6.1), discontinuations (4.4 vs 2.8), deaths (0.2 vs 0.4), herpes zoster (0.9 vs 0.7), malignancies (1.0 vs 0.9), major adverse cardiovascular events (0.3 vs 0.4), and venous thromboembolism (0.1 vs 0.1). Conclusion Deucravacitinib demonstrated persistent efficacy and consistent safety profiles in patients with psoriasis for up to 2 years after initial randomisation in the POETYK PSO-1, PSO-2, and LTE trials. References [1]Mease PJ et al. Efficacy and Safety of Selective TYK2 Inhibitor, Deucravacitinib, in a Phase 2 Trial in Psoriatic Arthritis. Ann Rheum Dis. (In Press). [2]Armstrong A et al. Presented at American Academy of Dermatology Virtual Meeting Experience 2021; April 23-25, 2021. Acknowledgements This study was sponsored by Bristol Myers Squibb. Writing and editorial assistance was provided by Lisa Feder, PhD, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, funded by Bristol Myers Squibb. Disclosure of Interests Richard B. Warren Consultant of: AbbVie, Almirall, Amgen, Astellas, Boehringer Ingelheim, Celgene, DiCE, Eli Lilly, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Pfizer, Sanofi, UCB, UNION, and Xenoport, Grant/research support from: AbbVie, Almirall, Amgen, Celgene, Janssen, Eli Lilly, Leo Pharma, Novartis, Pfizer, UCB, Howard Sofen Consultant of: Clinical investigator: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis, and Sun Pharma., Shinichi Imafuku Grant/research support from: Grants and personal fees: AbbVie, Eisai, Kyowa Kirin, Janssen, Leo Pharma, Maruho, Sun Pharma, Taiho Yakuhin, Tanabe Mitsubishi, and Torii Yakuhin; Personal fees: Amgen (Celgene), Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Novartis, and UCB, Jacek Szepietowski Consultant of: Advisory board member/consultant: AbbVie, Leo Pharma, Novartis, Pierre-Fabre, Sanofi Genzyme, and Trevi; Speaker: AbbVie, Eli Lilly, Janssen-Cilag, Leo Pharma, Novartis, and Sanofi Genzyme; Investigator: AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Galderma, Incyte, InfraRX, Janssen-Cilag, Manlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, UCB, and Trevi, Andrew Blauvelt Consultant of: Scientific adviser and/or clinical study investigator: AbbVie, Abcentra, Aligos, Almirall, Amgen, Arcutis, Arena, Aslan, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, EcoR1, Eli Lilly, Evommune, Forte, Galderma, Incyte, Janssen, Landos, Leo Pharma, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, UCB, and Vibliome, Lynda Spelman Consultant of: Consultant, paid investigator, and/or speaker: AbbVie, Amgen, Anacor, Ascend, Astellas, AstraZeneca, Blaze Bioscience, Bristol Myers Squibb, Boehringer Ingelheim, Botanix, Celgene, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Hexima, Janssen, Leo Pharma, Mayne, Medimmune, Merck (MSD), Merck-Serono, Novartis, Otsuka, Pfizer, Phosphagenics, Photon MD, Regeneron, Roche, Samumed, Sanofi Genzyme, SHR, Sun Pharma ANZ, Trius, UCB, and Zai Lab, Elizabeth Colston Shareholder of: Employee and shareholder: Bristol Myers Squibb, Employee of: Employee and shareholder: Bristol Myers Squibb, Jessica Toms Shareholder of: Employee and shareholder: Bristol Myers Squibb, Employee of: Employee and shareholder: Bristol Myers Squibb, Alex Buck Employee of: Contractor (through functional service provider Cytel): Bristol Myers Squibb, Subhashis Banerjee Shareholder of: Employee and shareholder: Bristol Myers Squibb, Employee of: Employee and shareholder: Bristol Myers Squibb, Alan Menter Consultant of: Advisory board: Abbott Labs, Amgen, Boehringer Ingelheim, Janssen Biotech, Leo Pharma; consultant: Abbott Labs, Amgen, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Honoraria: Abbott Labs, Amgen, Boehringer Ingelheim, Eli Lilly, Janssen Biotech, Leo Pharma, Novartis, Sun Pharma, and UCB; Investigator: Abbott Labs, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen Biotech, Leo Pharma, Merck, Novartis, Sun Pharma, and UCB; Research grants: Abbott Labs, Amgen, Boehringer Ingelheim, Celgene, Janssen Biotech, Leo Pharma, Merck, and Sun Pharma; Speaker: Abbott Labs, Amgen, Janssen Biotech, Leo Pharma, Sun Pharma, and UCB